We request funding to acquire a 800 MHz cryoprobe accessory. We have secured funding for a new 800 MHz instrument that will alleviate the long waiting times for and insufficient access to high-field instrumentation. The high-field instruments operating at 750 MHz and above available to the group of investigators asking for this support (Gerhard Wagner, James Chou, Christopher Walsh, Ellis Reinherz and Anders Naar) are limited to one 750 MHz spectrometer and half of a 900 MHz system. Despite this limited access, this group was very successful in determining structures and performing functional studies of very large and challenging systems, such as membrane proteins, complexes of translation initiation factors, non-ribosomal peptide synthetases, transcriptional activator/coactivator complexes, T-cell protein complexes and many more. Numerous new projects are in the pipeline but progress is slowed down due to the lack of access to high field instruments, and waiting times are often two months to get access to the 750 or 900 MHz spectrometers. To alleviate this, we have obtained funds to purchase a non-shielded 800 MHz spectrometer from a Harvard internal competition, and other sources, and we have secured funds to renovate space at the Harvard/MIT Center for Magnetic Resonance to house the new instrument. However, the funds available are only sufficient to purchase the spectrometer with a conventional room temperature probe and are not enough to buy a cryogenic probe. To optimally use the power of this new instrument we ask for funds for a cryoprobe accessory with one cryoplatform and two triple-resonance cryoprobes that are optimized for 1H detection (TCI), which will be the work horse for 3D ad 4D dispersed NOESY experiments, and a 13C/15N detection optimized probe, which will be used for novel experiments that promise to push the limit for studying very large system.
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